William F. Dove and colleagues
McArdle Laboratory for Cancer Research
1400 University Avenue
Madison, WI 53706-1599
Phone: (608) 262-0982

CV for William F. Dove

Research Description:
Our laboratory studies the genetic, cellular and molecular aspects of intestinal cancer. To pursue this goal, we have established two complementary animal models for inherited (familial) colon cancer - the Min (Multiple intestinal neoplasia) mouse and Pirc (Polyposis in rat colon) rat. These animal models, as well as mouse and rat strains specifically derived from them, display distinct cancer phenotypes (observable traits) and many of these phenotypes are also present in human cancer. For example, some human colon cancers continue to grow while others remain unchanged in size (static) for years, or even regress without intervention. Each of these fates (growth, stasis and regression) are observed among our animal models, by following tumors over time using colonoscopies in live animals. By manipulating the animal genetic backgrounds of these models, we can discover genes that influence colon cancer phenotypes such as tumor fate. Examining whole tissue sections helps us to identify, at the molecular or cellular level, the salient differences between tumors of different fates. Using molecular markers for cell death (apoptosis) or cell division, we can discover whether more cells undergo apoptosis in regressing tumors or whether fewer cells divide in tumors that are static. The microenvironment of the tumor is also important. For example, using cellular markers for tumor-associated leukocytes, we can ask whether there are different leukocyte populations in growing versus regressing tumors. These questions lie at the center of understanding the biology of colon cancer in humans. They can be experimentally addressed in our laboratory by appropriate use of our two sets of animal models.

An undergraduate in our laboratory begins by learning the duties that form the foundation crucial to a research laboratory. Our science relies greatly on the ability of our students to perform these tasks correctly and in a timely manner. As our undergraduate students acquire increased knowledge and skills they may become involved in a project with one of our doctoral or postdoctoral members. Undergraduates in our lab learn the fundamental biology of the colon, intestinal cancer and our mouse and rat models.

A doctoral or postdoctoral member of our laboratory learns the biology and genetics of the laboratory mouse and rat, objective assessment of neoplastic growth and regression, and the assay of molecular markers of neoplastic development within the tumor and its associated microenvironment. The emergent ability to knock out a gene of interest in the mouse or rat creates a powerful avenue to study the function of that gene in both the tumor and its host. Group members broaden their research capacity through our ongoing interactions with collaborators on campus. Working with faculty in biostatistics, we become familiar with the detection of quantitative modifiers of tumor susceptibility. Working with faculty in radiology and medical physics, we explore new imaging methods. With the Biotechnology Center we engage the evolving power of mass spectrometry in the analysis of protein markers expressed in the serum or plasma of tumor-bearing animals.

Altogether, uniquely complementing other investigations worldwide, our Wisconsin team hopes to achieve a deep understanding of the biology of colon cancer and thereby to impact its management in humans through diagnosis, prognosis, and early detection.